DNA sequences which encode immunoreactive HCMV-specific peptides

ABSTRACT

The invention relates to a DNA sequence which encodes three specific human cytomegalovirus (HCMV) peptides of the pp150 protein. These peptides are shown to have novel immunogenic properties. The DNA sequence is also used in a method of hybridization for the detection of fully complementary sequences.

This is a division of application Ser. No. 08/388,883, filed Feb. 13,1995, which is a continuation of application Ser. No. 08/200,305, filedFeb. 23, 1994, abandoned, which is a continuation of application Ser.No. 07/936,219, filed Aug. 27, 1992, abandoned.

The invention relates to peptides for the immunochemical determinationof human cytomegalovirus (HCMV)-specific antibodies and HCMV antigens,and to agents suitable for this method and to the use thereof.

Used to date in diagnosis to check the HCMV immunity status has been,for example, an enzyme immunoassay. This assay detected antibodiesspecifically directed against HCMV. The antigen employed was virusmaterial which was generally grown on human fibroblasts in an elaboratecell culture and, after processing, attached to a surface utilizable indiagnosis, for example an ELISA microtiter plate.

Obtaining HCMV antigen for antibody detection from cell culture isgenerally very time-consuming and costly and is associated with apossible risk of infection for the people engaged therein. To use thisantigen in an immunological diagnostic assay, the virus must be obtainedfrom the cell culture medium or even from the cells themselves or atleast be presented in a form which makes an immunological reactionpossible. Since further purification of this material by biochemicalmethods is very elaborate and involves large losses, for examplecell-bound virus material is only liberated by ultrasonification and isemployed directly after dilution for coating microtiter plates, forexample. In this case it is not only virus-specific structures which arebound to the surfaces of the microtiter plate wells but also to agreater extent cell-specific proteins. The latter in turn may withcertain diseases, for example autoimmune diseases, easily lead tofalse-positive results and accordingly to misdiagnosis. To determine thenumber of false-positive signals, generally investigation material fromnon-infected cell cultures is therefore used as control. This inevitablydoubles the complexity of the assay and the costs per sample.

A distinct improvement in the described method is represented by the useof recombinant proteins which can be prepared in high yield in aheterologous system, for example in Escherichia coli. Possible HCMVinfection is generally ruled out by cloning and expression of definedregions of the virus. In addition there is a possibility of adifferential diagnosis directed at specific virus proteins. However, toemploy recombinant proteins in immunological assays it must be ensuredthat no contaminating constituents of the host cell lead tofalse-positive reactions with serum samples. Specific, usually veryelaborate purification methods are needed in this case to achieve thisquality.

Furthermore, the recombinant proteins must carry immunologicallyreactive epitopes which unambiguously define the immune status and havea diagnostic relevance or a relevance for the production of a protectivestatus (vaccine). In most cases these epitopes cannot be prepared innative form by recombinant techniques because they represent foreignproteins for most of the expression systems used and rapidly undergoproteolytic degradation. For this reason they are usually expressed ashybrid proteins, with a host-protein for example β-galactosidase in thecase of Escherichia coli, as fusion partner stabilizing the expressionproduct. However, this foreign portion of the fusion may, owing to thefollowing purification steps, give rise to false-positive reactionswhich impede the diagnostic use of recombinant proteins.

A protein has now been identified which is generally suitable fordetermining the immune status for HCMV. For this protein, the proteinpp150, both the complete DNA sequence as well as a section 162 aminoacids long (the XhoI-PstI restriction fragment, called pXP1 cloned asplasmid) are known which contains sequences relevant for unambiguousdiagnosis (Jahn, G. et al. (1987), J. Virol. 61, 1358-1367).

J. Novak et al. (J. Novak et al. (1991), J. Gen. Virol. 72, 1409-1413)have now found, with the aid of synthetically prepared peptides, on thecomplete pp150 protein only three immunoreactive regions, of which tworegions are located between the cleavage sites of the restrictionendonucleases XhoI and PstI (XP1 region, Tab. 1).

The amino acids are reproduced in Tab. 1 as single letter code accordingto the following key: Ala=A, Arg=R, Asn=N, Asp=D, Cys=C, Gln=Q, Glu=E,Gly=G, His=H, Ile=I, Leu=L, Lys=K, Met=M, Phe=F, Pro=P, Ser=S, Thr=T,Trp=W, Tyr=Y and Val=V.

The object on which the present invention was based was first to developan assay with which it is possible to detect HCMV infections as early aspossible and with high specificity.

Surprisingly, it has now been found, that it was not possible to confirmthe immunoreactive regions found by Novak et al. on the XP1 region but,instead of this, three immunoreactive regions different from Novak etal. were found. It was additionally found that virtually completedetermination of the immune status is possible in particular by usingall three epitopes according to the invention in an immunoassay.

The invention therefore relates to peptides which react specificallywith antibodies against HCMV, and which contain at least one of thefollowing amino-acid sequences:

AS_(e) -gly ala gly ala ala ile leu-BS_(m) (peptide 1) (SEQ ID NO:1)

CS_(n) -arg ala trp ala leu-DS_(o) (peptide 2) (SEQ ID NO:2) and/or

ES_(p) -ala ser arg asp ala ala-FS_(q) (peptide 3) (SEQ ID NO:3)

where AS, BS, CS, DS, ES and FS are, independently of one another, anyappropriate amino acid and

    ______________________________________                                        e           are, independently of one another, integers                                   from 0 to 22,                                                     m           are, independently of one another, integers                                   from 0 to 25,                                                     n and o     are, independently of one another, integers                                   from 0 to 18                                                      and                                                                           p and q     are, independently of one another, integers                                   from 0 to 11.                                                     ______________________________________                                    

Preferred peptides are

    __________________________________________________________________________    for peptide 1:                                                                1.1 (SEQ ID NO: 4)                                                            ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                          1.2 (SEQ ID NO: 5)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                    pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    1.3 (SEQ ID NO: 6)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                    pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                               1.4 (SEQ ID NO: 7)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                    val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                    val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                1.5 (SEQ ID NO: 8)                                                            pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                    ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                    thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                            1.6 (SEQ ID NO: 9)                                                            pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                    ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                    thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH.sub.2                                                 1.7 (SEQ ID NO: 10)                                                           val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                               1.8 (SEQ ID NO: 11)                                                           pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                         1.9 (SEQ ID NO: 12)                                                           val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                    pro                                                                              thr                                                                              phe                                                                     1.10 (SEQ ID NO: 13)                                                          pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                                                              pro                                                                              thr                                                                              phe                                    ala                                                                              gly                                                                              thr                                                                     1.11 (SEQ ID NO: 14)                                                          gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                    leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                    ala                                                                              pro                                                                              NH.sub.2                                                                1.12 (SEQ ID NO: 15)                                                          gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                    ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                                                              pro                                                                              thr                                                                              phe                                                                              ala                                                                              gly                                    thr                                                                              gln                                                                              thr                                                                              pro                                                                  1.13 (SEQ ID NO: 16)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              gly                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                       1.14 (SEQ ID NO: 17)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                    pro                                                                              thr                                                                              phe                                                                              ala                                                                              gly                                                                              thr                                                                              gln                                                                              thr                                                                              pro                                                   1.15 (SEQ ID NO: 18)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH.sub.2                               1.16 (SEQ ID NO: 19)                                                          gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                    leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                    ala                                                                           for peptide 2:                                                                2.1 (SEQ ID NO: 20)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                             2.2 (SEQ ID NO: 21)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                            2.3 (SEQ ID NO: 22)                                                           pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                    pro                                                                              his                                                                              leu                                                                     2.4 (SEQ ID NO: 23)                                                           pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                    pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                            2.5 (SEQ ID NO: 24)                                                           trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                    ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                                                              arg                                                            2.6 (SEQ ID NO: 25)                                                           glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                    pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                                                              thr                                                                              thr                                                         2.7 (SEQ ID NO: 26)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                           2.8 (SEQ ID NO: 27)                                                           ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                    his                                                                              leu                                                                              ala                                                                     2.9 (SEQ ID NO: 28)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                    thr                                                                              thr                                                                              ser                                                                              thr                                                                              ala                                                               2.10 (SEQ ID NO: 29)                                                          arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                    phe                                                                           for peptide 3:                                                                3.1 (SEQ ID NO: 30)                                                           pro                                                                              arg                                                                              ala                                                                              ala                                                                              val                                                                              thr                                                                              gln                                                                              thr                                                                              ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                                                              ala                                    3.2 (SEQ ID NO: 31)                                                           ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                                                              ala                                                                              asp                                                                              glu                                                                              val                                                                              trp                                                                              ala                                                                              leu                                                                              arg                                                                              asp                                    gln                                                                              thr                                                                              ala                                                                     __________________________________________________________________________     Of these, the following peptides are particularly preferred:                  for peptide 1:                                                                1.3 (SEQ ID NO: 16), 1.4 (SEQ ID NO: 17, 1.6 (SEQ ID NO: 4, 1.11 (SEQ ID      NO: 14, 1.13 (SEQ ID NO: 16)                                                  for peptide 2:                                                                2.1 (SEQ ID NO: 12), 2.5 (SEQ ID NO: 21), 2.9 (SEQ ID NO: 28) and/or 2.10     (SEQ ID NO: 24)                                                               for peptide 3:                                                                3.2 (SEQ ID NO: 31)                                                      

The expressions peptides and polypeptides are used for the purpose ofthe invention as equivalent to peptides and proteins with up to about 80AA.

By immunoreactive peptides are generally meant peptides with at leastone epitope, where the minimum length of the peptides is generallyapproximately 6, preferably approximately 8-10 amino acids.

It is often advantageous to derivatize peptides in a variety of ways,such as, for example, by amino-terminal or carboxy-terminal attachmentof one or more amino acids, preferably cysteine, in order, for example,to achieve linkage of peptides with one another or to a support. Theextensions generally comprise 1 to 40, preferably 1 to 20, in particular1 to 10 amino acids. Other examples are thioglycolic acid amidation,carboxy-terminal amidation such as, for example, with ammonia ormethylamine. Modifications of these types may alter the net charge onthe polypeptide and improve the physico-chemical properties of thepeptide or facilitate covalent bonding of the peptide to a solidsupport, to carrier protein or to another peptide.

It is furthermore also possible by replacing individual amino acids bystructurally related amino acids to generate immunoreactive mutants.Thus, for example, the amino acid al can be replaced by leu, ile oramino acids which do not occur naturally, such as nva.

In general, modifications of this type do not result in directionalterations in the immunoreactivity of a peptide, although it isperfectly possible to achieve improved immunological properties of thepeptides. Thus, for example, methionine is prone to spontaneousoxidation, which can be prevented by replacement by norleucine, withoutessentially changing the antigenic properties of the polypeptide.

Other amino-acid replacements can take place, for example, within thefollowing groups: gly, ala; val, ile, leu; asp, glu; asn, gln; ser, thr;lys, arg; phe, tyr; ala, ser; ala, thr; ala, val; ala, pro; ala, glu;leu, gln; gly, phe; ile, ser and ile, met.

The invention therefore also relates to peptides with an amino-acidsequence according to the invention modified by replacement, addition ordeletion of one or more amino acids.

It may likewise be advantageous to improve the polypeptide's propertiesof adsorption onto a support by the addition of a hydrophobic sequencecomprising about 2 to 20 hydrophobic amino acids such as, for example,phe ala phe ala phe (SEQ ID NO:32).

It has also been found that mixtures of the peptides according to theinvention may have better diagnostic properties than single peptides foran immunochemical anti-HCMV detection.

The invention therefore also relates to mixtures of the peptidesaccording to the invention.

Mixtures of peptides 1, 2 and 3 are particularly suitable, and in turnthe following mixtures are particularly preferred: 1.6, (SEQ ID NO:9)2.1, (SEQ ID NO:20) 3.2; (SEQ ID NO:31) 1.11, (SEQ ID NO:19) 2.1, (SEQID NO:20) 3.2; (SEQ ID NO:31) 1.6, (SEQ ID NO:9) 2.10, (SEQ ID NO:29)3.2; (SEQ ID NO:29) 1.11, (SEQ ID NO:14) 2.10, (SEQ ID NO:29) 3.2; (SEQID NO:31) 1.6, (SEQ ID NO:9) 2.7, (SEQ ID NO:26) 3.2 (SEQ ID NO:31) or1.11, (SEQ ID NO:14) 2.7, (SEQ ID NO:26) 3.2 (SEQ ID NO:31).

However, if a mixture is prepared from the peptides and used to coat,for example, a microtiter plate, there is a risk of unequal coatingsince the peptides vary in their efficiency of binding to the surfaceowing to different physical properties.

In another embodiment, therefore, 2 or more of the said peptides,preferably 2 to 10, in particular 2 to 4, peptides are linked with orwithout spacer. This results in uniform coating of the microtiterplates. It is even possible to prepare polymeric forms of two or morepeptides by methods known to the person skilled in the art, so thatmultiple immunorelevant epitopes are present on one peptide. Thepeptides according to the invention can, as already mentioned, also bebound to a carrier such as, for example, protein or latex particle.Thus, particularly suitable as carrier or else as bridge are, forexample, human serum albumin and/or polylysine.

Modifications of these types generally alter the passive adsorption orproperty of covalent bonding to the solid phase in a beneficial way,have an advantageous effect on the coupling method or act more stronglyas antigen in the generation of polyclonal or monoclonal antibodiesdirected against the peptides.

The invention therefore also relates to peptides which are linkedtogether with or without bridge, or can also be bound to a carrier.

The said immunoreactive peptides can be prepared by synthesis or geneticmanipulation, preferably by synthesis by methods known to the personskilled in the art.

They can be synthesized both in the form of one peptide and in the formof a mixture of a plurality of small peptides with overlapping ornon-overlapping amino-acid sequence.

The polypeptides prepared by genetic manipulation also include fusionproteins whose fusion portion has subsequently been eliminated. Theyalso include polypeptides which can be modified where appropriate, forexample, by glycosylation, acetylation or phosphorylation.

Solid-phase synthesis, especially the Fmoc method of G. B. Fields and R.L. Noble has preferably been used for the chemical peptide synthesis.Using this method the peptides according to the invention can beprepared, for example, in a semiautomatic or completely automaticpeptide synthesizer on polystyrene (1% divinylbenzene) using anchorssuitable for Fmoc. A carboxyl or carboxamide functionality, for example,can be used at the C terminus. In the case of a carboxyl group it ispossible and preferable to use alkoxybenzyl alcohol as anchor on theresin. Peptide amides can be synthesized, for example, on(5-carboxylatoethyl-2,4-dimethoxyphenyl)-4'-methoxyphenyl!methylamineresin by the method of Breipohl et al. (G. Breipohl, J. Knolle and W.Stuber, Int. J. Peptide, Protein Res. 34, 1989, 252-267). The initialloadings of the resins were generally in the range 0.2-1.0 mmol,preferably 0.4-0.6 mmol of amino functionalities/gram. The syntheseswere carried out by the following general reaction sequence:

1. Resin washed, for example with DMF.

2. Resin treated with a solvent mixture such as, for example,piperidine/DMF.

3. Resin washed, preferably first with DMF/isopropanol and then withDMF.

4. Resin reacted with a 1-6-fold, preferably 2-4-fold, in particular2.5-3.5-fold, excess of activated amino-acid derivative, for example ofa Fmoc-activated amino acid. The amino-acid derivative was activated,for example, with DIC/HOBt or TBTU/DIPEA in DMF.

5. Reaction steps 3 and 4 repeated.

After the required peptide had been synthesized the peptides werecleaved off the resin, for example by treatment with 90% TFA, 5%ethanedithiol, 5% resorcinol at room temperature. The peptide which hasbeen cleaved off can subsequently be crystallized from ether andpurified by general methods such as HPLC, ion exchange chromatography orgel permeation. The composition of the peptides can be checked byamino-acid analysis and/or mass spectrometry, and the purity can betested, for example, by HPLC.

Bridged peptides were likewise prepared by generally known methods. Thefollowing possibilities, inter alia, exist for the bridging:

A) direct amide linkage;

B) bridging via a peptide with 1 to 10, preferably 1 to 5, in particular1-3, amino acids;

C) thioether or disulfide bridge.

The peptides bridged with an amino acid or a short peptide can besynthesized by the abovementioned method. An example of a suitable shortpeptide is a triglycine. Joining the two peptides via a so-calledspacer, in particular via a hydrophobic spacer, generally has, asalready mentioned, a beneficial effect on the interaction of themicrotiter plate. A particularly preferred amino acid as bridgingelement is, for example, epsilon-amino-caproic acid.

Thioether or disulfide bridges are obtained by synthesizing a maleimidefunctionality at the N terminus of one peptide and introducing asulfhydryl group, preferably in the form of cysteine, at the C or Nterminus of the other peptide, and subsequently linking the twopeptides. This linkage can take place both on a solid support and insolution.

An immunochemical detection generally comprises methods which permit thedetermination of antigens and/or antibodies in body fluids such as;serum, plasma, saliva, cerebrospinal fluid or urine as homogeneous (insolution) or heterogeneous (with solid phase) methods. These are alsocalled immunoassays, and examples are enzyme immunoassay (ELISA or EIA),radioimmunoassay (RIA), immunofluorescence assay (IFA),radioimmunoprecipitation assay (RIPA) or agar gel diffusion assay etc.

These numerous, very different methods differ in specific embodiments,in the marker used for detection or measuring principle (for examplephotometrically, radio-metrically, visually or by aggregation, scatteredlight or precipitation behavior) and in the solid phases. The personskilled in the art is aware that separation of bound and free sampleantibodies or antigen is, although widely used, not absolutely necessarysuch as, for example, in so-called homogeneous assays. Heterogeneousimmunoassays are preferred, especially heterogeneous ELISA methods.

The antibody detection in an immunochemical detection method entailscontacting the sample with the described peptide sequences during theprocedure, in order to form an antigen-antibody complex in a particularstep of the relevant method, or to prevent the formation thereof incompetitive and inhibition assays by adding suitable labeled reagents.

The invention therefore also relates to an immunochemical method for thedetection and/or for the determination of HCMV antibodies using thepeptides according to the invention and to an assay kit therefor.

In the direct methods, the antibodies can be contacted with peptidesbound to a solid phase or with labeled peptides or with both, it beingirrelevant whether the fundamental method is based as 1-, 2- ormultistep method on the principle of the second antibody assay or on theimmunometric assay design (double-antigen sandwich) either withidentical or different peptides (or peptide mixtures) on the solid phaseand as liquid reagent for the detection and in conjunction with specificso-called capture antibodies (for example anti-IgM) or affinity reagents(for example protein A).

The peptides can be linked to the solid phase covalently, by adsorptionor by means of specific antibodies or similar affinity methods, forexample via the biotin/avidin complex, but adsorption is preferred.

Suitable as support material for the solid phase are plastics such aspolystyrene, polyvinyl chloride, polyamide and other synthetic polymers,natural polymers such as cellulose and derivatized natural polymers suchas cellulose acetate and nitrocellulose, as well as glass, especially asglass fibers. Polystyrene is preferred as support material.

The supports can be in the form of beads, rods, tubes and microtiterplates or in the form of suspensions such as, for example, latexparticles. Sheet-like structures such as paper strips, disks andmembranes are likewise suitable. The surface of the supports can be bothpermeable and impermeable to aqueous solutions.

Preferred supports are beads, tubes, wells, micro-particles, paperstrips and membranes. Particularly preferred supports are microtiterplates, latex particles, polystyrene beads or magnetically attractableparticles.

The peptide concentration for coating the support is generally about0.01-20 μg/ml, preferably 0.01-10 μg/ml particularly preferably 2-10μg/ml.

It is particularly advantageous to use synthetically preparedpolypeptides whose high purity and strong antigenicity allows very smallamounts to be used, for example 0.01-2.0 μg/ml, preferably 0.1-0.5μg/ml. The binding capacity of the support, in particular whenpolystyrene is used, is generally not saturated so that it is normallypossible to coat with a plurality of different polypeptides, inparticular with 2-5, especially with 3-4, different polypeptides, whichis a particular advantage.

When the peptides are used as labeled derivatives for the detection, allcoupling techniques known to the person skilled in the art are suitable.It is also possible to apply multistage methods such as, for example,preformed peptide-antibody complexes in which the antibody carries thelabeling, or high-affinity systems such as, for example, biotin/avidinwith labeling of one of these reactants.

Examples of markers which can be used are radioactive isotopes,fluorescent or chemiluminescent dyes. Markers which can also be used areenzymes which, for example, are detected by chromogenic, luminogenic orfluorogenic substrate systems or by subsequent amplifier systems with asecond enzyme which is activated by the first.

The markers preferably used are enzymes, especially the alkalinephosphatase and/or horseradish peroxidase or chemiluminoqenic compoundssuch as, for example, acridinium esters.

The labeling is carried out by methods which are described in the priorart for the said markers. In the case of labeling of the antibodies withperoxidase it is possible to use the periodate technique of NAKANE etal., 1974, J. Histochem. Cytochem. 22, 1084-1090, or a method ofISHIKAWA et al., 1983, J. Immunoassay 4, 209-327, in which the partnersare linked by a heterobifunctional reagent.

Besides these methods it is possible to use the peptides for sensitizingsuitable surfaces such as, for example, latex or erythrocytes in orderto measure automatically or visually the physicochemical changes inducedby peptide-specific antibodies, such as, for example, precipitations,aggregation or light scattering. It is known that it is also possible toemploy the peptides underivatized for the inhibition of thesemeasurement principles as well as the abovementioned methods.

The antigens can be detected using immunodiagnostic methods which makeuse of polyclonal or monoclonal antibodies which are prepared using thepeptides according to the invention or derivatives thereof. Theembodiments suitable for the detection method are known to the personskilled in the art and comprise formation in a particular step ofantibody-antigen complexes or inhibition of complex formation incompetitive methods by adding a labeled antigen.

The invention therefore also relates to an immunochemical method for thedetection and/or determination of HCMV antigen using antibodies againstthe peptides according to the invention, and the assay kit therefor.

Suitable as solid phases, markers or measurement principle for theestablishment of an antigen assay are all the possibilities explainedfor the corresponding antibody determination, with the competitiveprinciple and the double antibody sandwich technique being particularlypreferred as immunochemical method. It is immaterial in this connectionwhether the methods are designed as 1-, 2- or 3-step methods. Thus,multistep methods can be carried out with unlabeled detection antibodieswhich are determined with the aid of another antibody which is directedagainst them and is appropriately labeled. It is advantageous for thegeneration of the antibodies to modify the peptides in such a way thattheir immunogenic property is improved as is possible, for example, bycoupling to natural proteins, such as, for example, to serum proteinssuch as gamma globulin or serum albumin, to hemocyanins such asKLH=keyhole limpet hemocyanin or toxoids such as diphtheria or tetanustoxoid (B. S. Schaffhausen in Hybridoma Technologie in the Biosciencesand Medicine, ed. T. A. Springer, Plenum Press NY, London 1985).

Finally, the present invention can also be applied when using animmunodiagnostic element which contains the solid phase and, in dryform, a part or else all of the reagents required, and in this case toothe new peptides are either present on the solid phase or in thedetection reagent or in both, and an antibody determination, an antigendetection or combinations with other analytes is carried out.

The peptides according to the invention can be tested by, for example,coating a microtiter plate with the peptides. The coating is generallycarried out in a buffer solution, for example in a carbonate, phosphateor trishydroxymethylaminomethane buffer, preferably in a carbonatebuffer. After the coating, the plates were incubated with serum samplesin a dilution of 1:1 to 1:250, preferably 1:1 to 1:10, in particular1:1.5 to 1:2.5. Subsequently the antigen-antibody complex was detectedby the methods indicated above, for example using a labeled secondantibody against the antigen-antibody complex (immunoassay).

The invention also relates to an immunochemical method and a combinationkit therefor for the detection and/or for the determination of aplurality of different antibody specificities each against differentpathogens, wherein one or more of the HCMV peptides according to theinvention and one or more immunoreactive peptides from other pathogensare immobilized on a support, and the antibodies against them aredetected by the abovementioned methods, differentially ornon-differentially, preferably differentially.

It is possible to employ in the combination assay virus species relatedto HCMV, such as, for example, the herpes viruses herpes simplex 1and/or 2 (HSV 1/2), Epstein-Barr virus (EBV), varicella zoster virus(VZV) or human herpes virus 6 (HHV 6) and/or unrelated virus speciessuch as, for example, the hepatitis viruses HAV, HBV, HCV or else theviruses HIV1 and HIV2. In particular, it is possible to employ mixturesof HCMV peptides and one or more peptides and/or recombinant proteins ofother pathogens in the combination assay, in which case the peptidesought not to have any measurable cross-reactivity with one another.

The peptides according to the invention, the immunoreactive parts andmutants thereof are suitable, for example, for HCMV diagnosis andvaccination. The peptides can also be used as coating antigens forvarious diagnostic assay systems which operate with various surfaces,for example enzyme immunoassay, magnetic and latex particles, teststrips, films and papers manufactured in various ways etc.

One advantage of the immunoreactive peptides according to the inventionis a high sensitivity and specificity for the detection of HCMVantibodies so that, besides diluted, it is also possible to useundiluted or only slightly diluted samples. Another advantage of thepeptides is that, because of their relatively short sequence length,they can be chemically synthesized simply and in high yield. Chemicalsynthesis has the advantage that the synthetic peptides are free ofcell-specific proteins.

The invention furthermore relates to DNA sequences which code for atleast one of the peptides according to the invention.

The invention also relates to an analytical method for the detectionand/or for the determination of HCMV, wherein a hybridization reactionwhich uses at least one nucleic acid probe which in its specific part iscomplementary to at least one of the DNA sequences according to theinvention is employed as specific step.

The invention also relates to polyclonal and/or mono-clonal antibodieswhich are directed against one or more of the peptides according to theinvention. The antibodies can be obtained by immunization of a suitabledonor, for example a rabbit, with the peptides according to theinvention by generally known methods.

The invention also relates to vaccines against HCMV which contain atleast one of the peptides according to the invention or antibodiesagainst them.

The invention also relates to an immunoassay which contains at least oneof the peptides according to the invention, in particular aheterogeneous immunoassay.

    ______________________________________                                        List of abbreviations                                                         ______________________________________                                        DIC      Diisopropylcarbodimide                                               DIPEA    Diisopropylethylamine                                                DMF      Dimethylformamide                                                    Bop      1-Benzotriazolyloxytris(dimethylamino)phosphonium                             hexafluorophosphate                                                  Fmoc     Fluorenylmethoxycarbonyl                                             HOBt     Hydroxybenzotriazole                                                 TBTU     2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyl-                                 uronium tetrafluoroborate                                            ______________________________________                                    

The following examples are intended to explain the invention in detailwithout, however, restricting it thereto:

EXAMPLES

1. Preparation of gly ala gly val asn val pro ala gly ala gly ala alaile leu thr pro thr pro val asn pro ser thr ala pro ala pro alapro-amide (peptide 1.11)(SEQ ID NO:14)

1.06 g of Fmoc-amide anchor resin were reacted in a completely automaticpeptide synthesizer (Advanced ChemTech^(R), Louisville, Ky. USA) inaccordance with the manufacturer's instructions. The amino-acid excesswas 3-fold. The reaction time per amino-acid derivative was 30 minutes.506 mg of Fmoc-proline was employed, together with 213 mg of HOBt and697 mg of Bop (in place of TBTU), as first amino acid. 3 Mmol ofdiisopropylethylamine were added as base. The carboxamide functionalitywas derivatized with trityl. The synthesis was carried out by thefollowing reaction sequence (for 1 g of resin):

1 Resin washed 3 times with 15 ml of DMF each time

2 Resin treated with 15 ml of 20% piperidine/DMF (3 min)

3 Resin treated with 15 ml of 20% piperidine/DMF (10 min)

4 Resin washed 3 times alternately with DMF/isopropanol

5 Resin washed twice with DMF

6 Amino-acid derivative introduced in 3-fold excess and activated eitherwith DIC/HOBt or with TBTU/DIPEA in DMF and shaken with the resin for 30min

7 Resin washed twice alternately with DMF/isopropanol

At the end of the coupling reactions, the peptide resin was washed withmethanol and diethyl ether and dried under high vacuum. 2.36 grams ofpeptide resin were stirred with 27 ml of trifluoroacetic acid/1.5 gramof resorcinol/1.5 ml of ethanedithiol at room temperature for 1.5 hoursand crystallized in diethyl ether. The crude peptide was washed withdiethyl ether and dried under high vacuum (yield 1090 mg). The peptidewas chromatographed on Sephadex G-25 in 0.5% acetic acid, and thepeptide fraction was isolated by freeze drying (yield 654 mg). Thepurity of the substance was tested by HPLC. The correct. composition wasconfirmed by amino-acid analysis. The peptide content was 86%.

2. Testing of the peptides

A microtiter plate with 96 wells was coated with a synthesized peptide.To do this, a solution of 2.5 μg of peptide per ml of carbonate bufferwas made up and introduced in 100 μl portions into the wells for thecoating. The peptides were adsorbed onto the surfaces at 4° C. overnightand, after removal of the peptide solution, the wells were washedseveral times with washing buffer (50 mM Tris, pH 7.2, 10 mM EDTA, 0.2%Tween 20). Then individual human serum samples in a 1:2 dilution wereintroduced and incubated at 37° C. for 1 hour. After another washingstep, the conjugate antibody specific for human IgG antibodies or humanIgM antibodies and labeled with peroxidase was added and the mixture wasincubated at room temperature for 0.5 hour. The reaction wassubsequently stopped by adding 0.5M sulfuric acid and extinction of theindividual samples was measured at a wavelength of 450/650 nm in aphotometer.

3. Localization of relevant epitopes

To test the immunogenicity, peptides of various length from the completeamino-acid sequence region from 718 to 880 of the HCMV protein pp150(Tab. 2 and 3) were synthesized as described in Example 1. Subsequently,as in Example 2, the microtiter plates were coated with the synthesizedpeptides, and the immunological reactivity was assayed. The result ofthe series of assays was that all the tested HCMV-positive sera reactedin particular with at least one of the three specific sequence regions,whereas the other sequence regions showed only a weak immunologicalreaction (Tab. 2 and 3). The three immunologically reactive peptideshave the following sequences:

AS_(e) -gly ala gly ala ala ile leu-BS_(m) (peptide 1)(SEQ ID NO:1)

CS_(n) -arg ala trp ala leu-DS_(o) (peptide 2)(SEQ ID NO:2)

and/or

ES_(p) -ala ser arg asp ala ala-FS_(q) (peptide 3)(SEQ ID NO:3),

where AS, BS, CS, DS, ES and FS are, independently of one another, anyappropriate amino acid and

    ______________________________________                                        e           are, independently of one another, integers                                   from 0 to 22,                                                     m           are, independently of one another, integers                                   from 0 to 25,                                                     n and o     are, independently of one another, integers                                   from 0 to 18                                                      and                                                                           p and q     are, independently of one another, integers                                   from 0 to 11.                                                     ______________________________________                                    

It was possible in this way to differentiate sera which reacted eitherwith all or else only with one or two sequence regions.

Demonstrably HCMV-negative sera did not react with the three peptides.

4. Diagnostic use of the peptides according to the invention

In order to test the immunoreactivity of the peptides found, a mixtureof peptides 1.11, (SEQ ID NO:14) 2.10 (SEQ ID NO:29) and 3.2(SEQ IDNO:31)--total concentration 2.5 μg/ml with a mixing ratio of 1:1:1 (byweight)--were introduced as an antigen into microtiter plates as inExample 2, and the assay was carried out as described therein. Used inthis case was a defined and previously tested group of sera which hadalready been assayed in a conventional assay for IgM and IgG reactivity;reference assays: CMV Enzygnost^(R) IgM-POD and CMV Enzygnost^(R)IgG-POD, Behringwerke AG, Marburg. The indicated assay configuration isvery suitable for diagnosing the HCMV immune status both for IgM and forIgG antibody detection (Tab. 4 and 5).

5. Reaction of the monoclonal antibody 87-55/02 with one of theidentified peptide epitopes

A monoclonal antibody which has an unambiguous immunological reactionwith the HCMV protein pp150 and one with the recombinant protein sectionpXP1, measured as immunoblot and ELISA reactivity, was investigated onan ELISA microtiter plate which had been coated with various synthesizedpeptides in Table 3 at the same concentration (0.25 μg/well). Afterdevelopment of the plate with said antibody, the reaction with thepeptide 2.7, (SEQ ID NO:26) which had previously been identified as animportant epitope, was very clearly distinct. It was concluded from themethod for selecting the monoclonal antibody that the identified epitopemust have a very important structure which is not even destroyed bydenaturation of the complete protein. This monoclonal antibodycorrespondingly reacts both with the synthesized peptide 2.7 (SEQ IDNO:26) and with the recombinant protein XP1 (SEQ ID NO:33) and the pp150protein of HCMV.

                                      TABLE 1                                     __________________________________________________________________________    (SEQ ID NO: 33)                                                               Amino-acid sequence of XP1 (amino acid 718-880 of HCMV protein pp             __________________________________________________________________________    150)                                                                          1  DPRFTDTLVD                                                                            ITDTETSAKP                                                                            PVTTAYKFEQ                                                                            PTLTFGAGVN                                                                            VPAGAGAAIL                                 51 TPTPVNPSTA                                                                            PAPAPTPTFA                                                                            GTQTPVNGNS                                                                            PWAPTAPLPG                                                                            DMNPANWPRE                                 101                                                                              RAWALKNPHL                                                                            AYNPFRMPTT                                                                            STASQNTVST                                                                            TPRRPSTPRA                                                                            AVTQTASRDA                                 151                                                                              ADEVWALRDQ                                                                            TA                                                                 __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________    Individual reactivities of the synthetic peptides from the XP1 region of      the HCMV protein pp 150                                                       The individual reactivities of the synthetic pXP1 segments with the           assayed                                                                       group of CMV IgG-positive sere are reported in percent.                       __________________________________________________________________________    1. asp                                                                              pro                                                                              arg                                                                              phe                                                                              thr                                                                              asp                                                                              thr                                                                              leu                                                                              val                                                                              asp                                                                              ile                                                                              thr                                                                              asp                                    thr   glu                                                                              thr                                                                              ser                                                                              ala                                                                              lys                                                                              pro                                                                              pro                                                                              val                                                                              (SEQ ID NO: 34)                                 Reactivity 20%                                                                2. ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                                                              pro                                                                              thr                                                                              phe                                                                              ala                                                                              gly                                                                              thr                                    gln   thr                                                                              pro                                                                              val                                                                              asn                                                                              gly                                                                              asn                                                                              ser                                                                              (SEQ ID NO: 35)                                    Reactivity 20%                                                                3. ala                                                                              pro                                                                              thr                                                                              ala                                                                              pro                                                                              leu                                                                              pro                                                                              gly                                                                              asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                    (SEQ ID NO: 36)                                                               Reactivity 30%                                                                4. gln                                                                              asn                                                                              thr                                                                              val                                                                              ser                                                                              thr                                                                              thr                                                                              pro                                                                              arg                                                                              arg                                                                              pro                                                                              ser                                                                              thr                                    pro   arg                                                                              ala                                                                              ala                                                                              val                                                                              thr                                                                              gln                                                                              thr                                                                              ala                                                                              (SEQ ID NO: 37)                                 Reactivity 40%                                                                5. asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                       ala                                                                              leu                                                                     Reactivity 60%                                                                              (Peptide 2.7) (SEQ ID NO: 26)                                   6. arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                       pro                                                                              phe                                                                     Reactivity 80%                                                                              (Peptide 2.10) (SEQ ID NO: 29)                                  7. gly                                                                              thr                                                                              gln                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              gly                                                                              asn                                                                              ser                                                                              pro                                                                              trp                                                                              ala                                    pro   thr                                                                              ala                                                                              (SEQ ID NO: 38)                                                   Reactivity 20%                                                                8. pro                                                                              val                                                                              thr                                                                              thr                                                                              ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                    thr   phe                                                                              (SEQ ID NO: 39)                                                      Reactivity 10%                                                                9. leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                    gly   ala                                                                              ala                                                                              ile                                                                              leu                                                                              (SEQ ID NO: 40)                                             Reactivity 60%                                                                10.                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                    ala   (SEQ ID NO: 41)                                                         Reactivity 40%                                                                   pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                                                              thr                                                                              thr                                                                              ser                                                                              thr                                                                              ala                                                                              ser                                                                              gln                                                                              asn                                    thr   val                                                                              (SEQ ID NO: 42)                                                      Reactivity 60%                                                                   ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                                                              ala                                                                              asp                                                                              glu                                                                              val                                                                              trp                                                                              ala                                                                              leu                                                                              arg                                       asp                                                                              gln                                                                              thr                                                                              ala                                                               Reactivity 80%                                                                              (Peptide 3.2) (SEQ ID NO: 31)                                      gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                       ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                       ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH2                                                            Reactivity 90%                                                                              (Peptide 1.11) (SEQ ID NO: 14)                                     glu                                                                              thr                                                                              ser                                                                              ala                                                                              lys                                                                              pro                                                                              pro                                                                              val                                                                              thr                                                                              thr                                                                              ala                                                                              tyr                                                                              lys                                    phe   glu                                                                              (SEQ ID NO: 43)                                                      Reactivity 10%                                                                   lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                    (SEQ ID NO: 44)                                                               Reactivity 20%                                                                   ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                          (SEQ ID NO: 45)                                                               Reactivity 40%                                                                   val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                       (SEQ ID NO: 46)                                                               Reactivity 10%                                                                   his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                                                              thr                                                                              thr                                                                              ser                                    thr   ala                                                                              (SEQ ID NO: 47)                                                      Reactivity 60%                                                                   pro                                                                              arg                                                                              ala                                                                              ala                                                                              val                                                                              thr                                                                              gln                                                                              thr                                                                              ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                       ala                                                                        Reactivity 60%                                                                              (Peptide 3.1) (SEQ ID NO: 30)                                   20.                                                                              asp                                                                              pro                                                                              arg                                                                              phe                                                                              thr                                                                              asp                                                                              thr                                                                              leu                                                                              val                                                                              asp                                                                              ile                                          Reactivity 10%                                                                   ile                                                                              thr                                                                              asp                                                                              thr                                                                              glu                                                                              thr                                                                              ser                                                                              ala                                                                              lys                                                                              pro                                                                              pro                                                                              val                                                                              thr                                    thr   ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              (SEQ ID NO: 49)                              Reactivity 20%                                                                   ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                       pro                                                                              his                                                                              leu                                                                              ala                                                               Reactivity 70%                                                                              (Peptide 2.8) (SEQ ID NO: 27)                                      asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                       ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                       Reactivity 80%                                                                              (Peptide 2.1) (SEQ ID NO: 20)                                      pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                       gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                       pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH.sub.2                                        Reactivity 90%                                                                              (Peptide 1.6) (SEQ ID NO: 9)                                       ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                       gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                       thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                       ala                                                                              pro                                                                              NH.sub.2                                                             Reactivity 85%                                                                              (Peptide 1.15) (SEQ ID NO: 18)                                  __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________    Individual reactivities of particularly reactive peptides from the            XP1 region of the HCMV protein pp 150                                         The individual reactivities of the synthetic pXP1 segments with the           assayed group of CMV IgG-positive sera are reported in percent.               __________________________________________________________________________    Peptide No. 1                                                                 1.1 (SEQ ID NO: 4)                                                            ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                          Reactivity 80%                                                                1.2 (SEQ ID NO: 5)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                    pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    Reactivity 80%                                                                1.3 (SEQ ID NO: 6)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                    pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                               Reactivity 85%                                                                1.4 (SEQ ID NO: 7)                                                            phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                    pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                   Reactivity 90%                                                                1.5 (SEQ ID NO: 8)                                                            pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                    ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                    thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                            Reactivity 80%                                                                1.6 (SEQ ID NO: 9)                                                            pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                    gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                    ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH.sub.2                                              Reactivity 90%                                                                1.7 (SEQ ID NO: 10)                                                           val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                               Reactivity 70%                                                                pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                         Reactivity 70%                                                                1.9 (SEQ ID NO: 12)                                                           val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                    pro                                                                              thr                                                                              phe                                                                     Reactivity 70%                                                                1.10 (SEQ ID NO: 13)                                                          pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                    asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                                                              pro                                                                              thr                                                                              phe                                    ala                                                                              gly                                                                              thr                                                                     Reactivity 80%                                                                1.11 (SEQ ID NO: 14)                                                          gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                    leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                    ala                                                                              pro                                                                              NH2                                                                     Reactivity 90%                                                                1.12 (SEQ ID NO: 15)                                                          gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                    ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                                                              pro                                                                              thr                                                                              phe                                                                              ala                                                                              gly                                    thr                                                                              gln                                                                              thr                                                                              pro                                                                  Reactivity 80%                                                                1.13 (SEQ ID NO: 16)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                       Reactivity 90%                                                                1.14 (SEQ ID NO: 17)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              thr                                    pro                                                                              thr                                                                              phe                                                                              ala                                                                              gly                                                                              thr                                                                              gln                                                                              thr                                                                              pro                                                   Reactivity 60%                                                                1.15 (SEQ ID NO: 18)                                                          ala                                                                              tyr                                                                              lys                                                                              phe                                                                              glu                                                                              gln                                                                              pro                                                                              thr                                                                              leu                                                                              thr                                                                              phe                                                                              gly                                                                              ala                                                                              gly                                    val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                                                              leu                                                                              thr                                                                              pro                                    thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                                                              NH.sub.2                               Reactivity 85%                                                                1.16 (SEQ ID NO: 19)                                                          gly                                                                              ala                                                                              gly                                                                              val                                                                              asn                                                                              val                                                                              pro                                                                              ala                                                                              gly                                                                              ala                                                                              gly                                                                              ala                                                                              ala                                                                              ile                                    leu                                                                              thr                                                                              pro                                                                              thr                                                                              pro                                                                              val                                                                              asn                                                                              pro                                                                              ser                                                                              thr                                                                              ala                                                                              pro                                                                              ala                                                                              pro                                    ala                                                                           Reactivity 70%                                                                Peptide No. 2                                                                 2.1 (SEQ ID NO: 20)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                             Reactivity 80%                                                                2.2 (SEQ ID NO: 21)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                       ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                         Reactivity 75%                                                                2.3 (SEQ ID NO: 22)                                                           pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                       asn                                                                              pro                                                                              his                                                                              leu                                                                  Reactivity 70%                                                                2.4 (SEQ ID NO: 23)                                                           pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                       asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                         Reactivity 70%                                                                2.5 (SEQ ID NO: 24)                                                           trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                       leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                                                              arg                                                         Reactivity 80%                                                                2.6 (SEQ ID NO: 25)                                                           glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                       asn                                                                              pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                                                              thr                                                                              thr                                                      Reactivity 70%                                                                2.7 (SEQ ID NO: 26)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                       ala                                                                              leu                                                                        Reactivity 60%                                                                2.8 (SEQ ID NO: 27)                                                           ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                    his                                                                              leu                                                                              ala                                                                     Reactivity 70%                                                                2.9 (SEQ ID NO: 28)                                                           asp                                                                              met                                                                              asn                                                                              pro                                                                              ala                                                                              asn                                                                              trp                                                                              pro                                                                              arg                                                                              glu                                                                              arg                                                                              ala                                                                              trp                                                                              ala                                    leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                                                              phe                                                                              arg                                                                              met                                                                              pro                                    thr                                                                              thr                                                                              ser                                                                              thr                                                                              ala                                                               Reactivity 80%                                                                2.10 (SEQ ID NO: 29)                                                          arg                                                                              ala                                                                              trp                                                                              ala                                                                              leu                                                                              lys                                                                              asn                                                                              pro                                                                              his                                                                              leu                                                                              ala                                                                              tyr                                                                              asn                                                                              pro                                    phe                                                                           Reactivity 80%                                                                Peptide No. 3                                                                 3.1 (SEQ ID NO: 30)                                                           pro                                                                              arg                                                                              ala                                                                              ala                                                                              val                                                                              thr                                                                              gln                                                                              thr                                                                              ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                                                              ala                                    Reactivity 60%                                                                3.2 (SEQ ID NO: 31)                                                           ala                                                                              ser                                                                              arg                                                                              asp                                                                              ala                                                                              ala                                                                              asp                                                                              glu                                                                              val                                                                              trp                                                                              ala                                                                              leu                                                                              arg                                                                              asp                                    gln                                                                              thr                                                                              ala                                                                     Reactivity 80%                                                                __________________________________________________________________________

                  TABLE 4                                                         ______________________________________                                        IgM reactivity of the peptide mixture                                         Assessment      Reference assay                                                                           Peptide assay                                     ______________________________________                                        positive        22          21                                                negative        13          13                                                false-positive  0            0                                                false-negative  0            1                                                Number of IgM sera assayed: 35                                                Sensitivity:                  95.5%                                           Specificity:                 100%                                             ______________________________________                                    

                  TABLE 5                                                         ______________________________________                                        IgG reactivity of the peptide mixture                                         Assessment      Reference assay                                                                           Peptide assay                                     ______________________________________                                        positive        133         132                                               negative        152         149                                               false-positive  0            3                                                false-negative  0            1                                                Number of IgG sera assayed: 285                                               Sensitivity:                99.25%                                            Specificity:                98.03%                                            ______________________________________                                    

    __________________________________________________________________________    SEQUENCE LISTING                                                              (1) GENERAL INFORMATION:                                                      (iii) NUMBER OF SEQUENCES: 49                                                 (2) INFORMATION FOR SEQ ID NO:1:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 9 amino acids                                                     (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 1                                                               (D) OTHER INFORMATION: /note= "Xaa is ASe where AS is any                     appropriate amino acid and e is an integer from 0                             to 22."                                                                       (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 9                                                               (D) OTHER INFORMATION: /note= "Xaa is BSm, where BS is any                    appropriate amino acid, and m is an integer from 0                            to 25."                                                                       (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                       XaaGlyAlaGlyAlaAlaIleLeuXaa                                                   15                                                                            (2) INFORMATION FOR SEQ ID NO:2:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 7 amino acids                                                     (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 1                                                               (D) OTHER INFORMATION: /note= "Xaa is CSn where CS is any                     appropriate amino acid and n is an integer from 0                             to 25."                                                                       (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 7                                                               (D) OTHER INFORMATION: /note= "Xaa is DSo where DS is any                     appropriate amino acid and o is an integer from 0                             to 18."                                                                       (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                                       XaaArgAlaTrpAlaLeuXaa                                                         15                                                                            (2) INFORMATION FOR SEQ ID NO:3:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 8 amino acids                                                     (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 1                                                               (D) OTHER INFORMATION: /note= "Xaa is ESp where ES is any                     appropriate amino acid and p is an integer from 0                             to 11."                                                                       (ix) FEATURE:                                                                 (A) NAME/KEY: Region                                                          (B) LOCATION: 8                                                               (D) OTHER INFORMATION: /note= "Xaa is FSq where FS is any                     appropriate amino acid and q is an integer from 0                             to 11."                                                                       (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:                                       XaaAlaSerArgAspAlaAlaXaa                                                      15                                                                            (2) INFORMATION FOR SEQ ID NO:4:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                                       AlaTyrLysPheGluGlnProThrLeuThrPheGlyAlaGlyValAsn                              151015                                                                        ValProAlaGlyAlaGlyAlaAlaIleLeu                                                2025                                                                          (2) INFORMATION FOR SEQ ID NO:5:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 28 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                                       PheGluGlnProThrLeuThrPheGlyAlaGlyValAsnValProAla                              151015                                                                        GlyAlaGlyAlaAlaIleLeuThrProThrProVal                                          2025                                                                          (2) INFORMATION FOR SEQ ID NO:6:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 33 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                                       PheGluGlnProThrLeuThrPheGlyAlaGlyValAsnValProAla                              151015                                                                        GlyAlaGlyAlaAlaIleLeuThrProThrProValAsnProSerThr                              202530                                                                        Ala                                                                           (2) INFORMATION FOR SEQ ID NO:7:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 38 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                                       PheGluGlnProThrThrLeuThrPheGlyAlaGlyValAsnValPro                              151015                                                                        AlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsnProSer                              202530                                                                        ThrAlaProAlaProAla                                                            35                                                                            (2) INFORMATION FOR SEQ ID NO:8:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                                       ProThrLeuThrPheGlyAlaGlyValAsnValProAlaGlyAlaGly                              151015                                                                        AlaAlaIleLeuThrProThrProValAsnProSerThrAlaProAla                              202530                                                                        ProAla                                                                        (2) INFORMATION FOR SEQ ID NO:9:                                              (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 35 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                                       ProThrLeuThrPheGlyAlaGlyValAsnValProAlaGlyAlaGly                              151015                                                                        AlaAlaIleLeuThrProThrProValAsnProSerThrAlaProAla                              202530                                                                        ProAlaPro                                                                     35                                                                            (2) INFORMATION FOR SEQ ID NO:10:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 19 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                                      ValAsnValProAlaGlyAlaGlyAlaAlaIleLeuThrProThrPro                              151015                                                                        ValAsnPro                                                                     (2) INFORMATION FOR SEQ ID NO:11:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                                      ProAlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsnPro                              151015                                                                        SerThrAlaProAla                                                               20                                                                            (2) INFORMATION FOR SEQ ID NO:12:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 31 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                                      ValAsnValProAlaGlyAlaGlyAlaAlaIleLeuThrProThrPro                              151015                                                                        ValAsnProSerThrAlaProAlaProAlaProThrProThrPhe                                 202530                                                                        (2) INFORMATION FOR SEQ ID NO:13:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 31 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                                      ProAlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsnPro                              151015                                                                        SerThrAlaProAlaProAlaProThrProThrPheAlaGlyThr                                 202530                                                                        (2) INFORMATION FOR SEQ ID NO:14:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 30 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                                      GlyAlaGlyValAsnValProAlaGlyAlaGlyAlaAlaIleLeuThr                              151015                                                                        ProThrProValAsnProSerThrAlaProAlaProAlaPro                                    202530                                                                        (2) INFORMATION FOR SEQ ID NO:15:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                                      GlyAlaGlyAlaAlaIleLeuThrProThrProValAsnProSerThr                              151015                                                                        AlaProAlaProAlaProThrProThrPheAlaGlyThrGlnThrPro                              202530                                                                        (2) INFORMATION FOR SEQ ID NO:16:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 41 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:                                      AlaTyrLysPheGlyGlnProThrLeuThrPheGlyAlaGlyValAsn                              151015                                                                        ValProAlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsn                              202530                                                                        ProSerThrAlaProAlaProAlaPro                                                   3540                                                                          (2) INFORMATION FOR SEQ ID NO:17:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 51 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:                                      AlaTyrLysPheGluGlnProThrLeuThrPheGlyAlaGlyValAsn                              151015                                                                        ValProAlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsn                              202530                                                                        ProSerThrAlaProAlaProAlaProThrProThrPheAlaGlyThr                              354045                                                                        GlnThrPro                                                                     50                                                                            (2) INFORMATION FOR SEQ ID NO:18:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 41 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:                                      AlaTyrLysPheGluGlnProThrLeuThrPheGlyAlaGlyValAsn                              151015                                                                        ValProAlaGlyAlaGlyAlaAlaIleLeuThrProThrProValAsn                              202530                                                                        ProSerThrAlaProAlaProAlaPro                                                   3540                                                                          (2) INFORMATION FOR SEQ ID NO:19:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 29 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:                                      GlyAlaGlyValAsnValProAlaGlyAlaGlyAlaAlaIleLeuThr                              151015                                                                        ProThrProValAsnProSerThrAlaProAlaProAla                                       2025                                                                          (2) INFORMATION FOR SEQ ID NO:20:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 25 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:                                      AspMetAsnProAlaAsnTrpProArgGluArgAlaTrpAlaLeuLys                              151015                                                                        AsnProHisLeuAlaTyrAsnProPhe                                                   2025                                                                          (2) INFORMATION FOR SEQ ID NO:21:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:                                      AspMetAsnProAlaAsnTrpProArgGluArgAlaTrpAlaLeuLys                              151015                                                                        AsnProHisLeu                                                                  20                                                                            (2) INFORMATION FOR SEQ ID NO:22:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 17 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:                                      ProAlaAsnTrpProArgGluArgAlaTrpAlaLeuLysAsnProHis                              151015                                                                        Leu                                                                           (2) INFORMATION FOR SEQ ID NO:23:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:                                      ProAlaAsnTrpProArgGluArgAlaTrpAlaLeuLysAsnProHis                              151015                                                                        LeuAlaTyrAsn                                                                  20                                                                            (2) INFORMATION FOR SEQ ID NO:24:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:                                      TrpProArgGluArgAlaTrpAlaLeuLysAsnProHisLeuAlaTyr                              151015                                                                        AsnProPheArg                                                                  20                                                                            (2) INFORMATION FOR SEQ ID NO:25:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:                                      GluArgAlaTrpAlaLeuLysAsnProHisLeuAlaTyrAsnProPhe                              151015                                                                        ArgMetProThrThr                                                               20                                                                            (2) INFORMATION FOR SEQ ID NO:26:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:                                      AspMetAsnProAlaAsnTrpProArgGluArgAlaTrpAlaLeu                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:27:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 17 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:                                      AlaAsnTrpProArgGluArgAlaTrpAlaLeuLysAsnProHisLeu                              151015                                                                        Ala                                                                           (2) INFORMATION FOR SEQ ID NO:28:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 33 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:                                      AspMetAsnProAlaAsnTrpProArgGluArgAlaTrpAlaLeuLys                              151015                                                                        AsnProHisLeuAlaTyrAsnProPheArgMetProThrThrSerThr                              202530                                                                        Ala                                                                           (2) INFORMATION FOR SEQ ID NO:29:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:                                      ArgAlaTrpAlaLeuLysAsnProHisLeuAlaTyrAsnProPhe                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:30:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 14 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:                                      ProArgAlaAlaValThrGlnThrAlaSerArgAspAlaAla                                    1510                                                                          (2) INFORMATION FOR SEQ ID NO:31:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 17 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:                                      AlaSerArgAspAlaAlaAspGluValTrpAlaLeuArgAspGlnThr                              151015                                                                        Ala                                                                           (2) INFORMATION FOR SEQ ID NO:32:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 5 amino acids                                                     (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:                                      PheAlaPheAlaPhe                                                               15                                                                            (2) INFORMATION FOR SEQ ID NO:33:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 162 amino acids                                                   (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:                                      AspProArgPheThrAspThrLeuValAspIleThrAspThrGluThr                              151015                                                                        SerAlaLysProProValThrThrAlaTyrLysPheGluGlnProThr                              202530                                                                        LeuThrPheGlyAlaGlyValAsnValProAlaGlyAlaGlyAlaAla                              354045                                                                        IleLeuThrProThrProValAsnProSerThrAlaProAlaProAla                              505560                                                                        ProThrProThrPheAlaGlyThrGlnThrProValAsnGlyAsnSer                              65707580                                                                      ProTrpAlaProThrAlaProLeuProGlyAspMetAsnProAlaAsn                              859095                                                                        TrpProArgGluArgAlaTrpAlaLeuLysAsnProHisLeuAlaTyr                              100105110                                                                     AsnProPheArgMetProThrThrSerThrAlaSerGlnAsnThrVal                              115120125                                                                     SerThrThrProArgArgProSerThrProArgAlaAlaValThrGln                              130135140                                                                     ThrAlaSerArgAspAlaAlaAspGluValTrpAlaLeuArgAspGln                              145150155160                                                                  ThrAla                                                                        (2) INFORMATION FOR SEQ ID NO:34:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 22 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:                                      AspProArgPheThrAspThrLeuValAspIleThrAspThrGluThr                              151015                                                                        SerAlaLysProProVal                                                            20                                                                            (2) INFORMATION FOR SEQ ID NO:35:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:                                      AlaProAlaProAlaProThrProThrPheAlaGlyThrGlnThrPro                              151015                                                                        ValAsnGlyAsnSer                                                               20                                                                            (2) INFORMATION FOR SEQ ID NO:36:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 13 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:                                      AlaProThrAlaProLeuProGlyAspMetAsnProAla                                       1510                                                                          (2) INFORMATION FOR SEQ ID NO:37:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 22 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:                                      GlnAsnThrValSerThrThrProArgArgProSerThrProArgAla                              151015                                                                        AlaValThrGlnThrAla                                                            20                                                                            (2) INFORMATION FOR SEQ ID NO:38:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:                                      GlyThrGlnThrProValAsnGlyAsnSerProTrpAlaProThrAla                              151015                                                                        (2) INFORMATION FOR SEQ ID NO:39:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:                                      ProValThrThrAlaTyrLysPheGluGlnProThrLeuThrPhe                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:40:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:                                      LeuThrPheGlyAlaGlyValAsnValProAlaGlyAlaGlyAlaAla                              151015                                                                        IleLeu                                                                        (2) INFORMATION FOR SEQ ID NO:41:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 14 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:                                      IleLeuThrProThrProValAsnProSerThrAlaProAla                                    1510                                                                          (2) INFORMATION FOR SEQ ID NO:42:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:                                      ProPheArgMetProThrThrSerThrAlaSerGlnAsnThrVal                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:43:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:                                      GluThrSerAlaLysProProValThrThrAlaTyrLysPheGlu                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:44:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 13 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:                                      LysPheGluGlnProThrLeuThrPheGlyAlaGlyVal                                       1510                                                                          (2) INFORMATION FOR SEQ ID NO:45:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 11 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:                                      AlaGlyAlaAlaIleLeuThrProThrProVal                                             1510                                                                          (2) INFORMATION FOR SEQ ID NO:46:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 12 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:                                      ValAsnProSerThrAlaProAlaProAlaProThr                                          1510                                                                          (2) INFORMATION FOR SEQ ID NO:47:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:                                      HisLeuAlaTyrAsnProPheArgMetProThrThrSerThrAla                                 151015                                                                        (2) INFORMATION FOR SEQ ID NO:48:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 11 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:                                      AspProArgPheThrAspThrLeuValAspIle                                             1510                                                                          (2) INFORMATION FOR SEQ ID NO:49:                                             (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 23 amino acids                                                    (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                          (ii) MOLECULE TYPE: peptide                                                   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:                                      IleThrAspThrGluThrSerAlaLysProProValThrThrAlaTyr                              151015                                                                        LysPheGluGlnProThrLeu                                                         20                                                                            __________________________________________________________________________

We claim:
 1. An isolated and purified DNA fragment consisting of HCMVDNA sequence, wherein said HCMV DNA sequence is contained within the DNAencodingamino acids 718-880 of the HCMV protein pp150, and wherein saidHCMV DNA sequence encodes one or more peptides which react specificallywith antibodies against the HCMV pp150 protein, wherein said one or morepeptides are selected from the group consisting of:As_(e) -gly ala glyala ala ile leu-Bs_(m) (peptide 1)(SEQ ID NO:1), Cs_(n) -arg ala trp alaleu-Ds_(o) (peptide 2)(SEQ ID NO:2), and Es_(p) -ala ser arg asp alaala-Fs_(q) (peptide 3)(SEQ ID NO:3), where AS, BS, CS, DS, ES and FSare, independently of one another, any appropriate amino acid and e isan integer from 0 to 22, m is an integer from 0 to 25, n and o are,independently of one another, integers from 0 to 18, and p and q are,independently of one another, integers from 0 to
 11. 2. An analyticalmethod for the detection and/or for the determination of HCMV, whichcomprises:a) hybridizing at least one nucleic acid probe which is fullycomplementary to at least one of the DNA sequences as claimed in claim1; and b) detecting the presence and/or determining the amount of HCMV.3. The isolated and purified DNA fragment of claim 1 whereine is aninteger from 0 to 14, and m is an integer from 0 to
 19. 4. An analyticalmethod for the detection and/or for the determination of HCMV, whichcomprises:a) hybridizing at least one nucleic acid probe which is fullycomplementary to at least one of the DNA sequences as claimed in claim3; and b) detecting the presence and/or determining the amount of HCMV.